Resting-state functional connectivity, cortical GABA, and neuroactive steroids in peripartum and peripartum depressed women: a functional magnetic resonance imaging and spectroscopy study.
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Abstract
Postpartum depression (PPD) is associated with abnormalities in resting-state functional connectivity (RSFC) but the underlying neurochemistry is unclear. We hypothesized that peripartum GABAergic neuroactive steroids (NAS) are related to cortical GABA concentrations and RSFC in PPD as compared to healthy comparison women (HCW). To test this, we measured RSFC with fMRI and GABA+/Creatine (Cr) concentrations with proton magnetic resonance spectroscopy (1 H MRS) in the pregenual anterior cingulate (pgACC) and occipital cortices (OCC) and quantified peripartum plasma NAS. We examined between-group differences in RSFC and the relationship between cortical GABA+/Cr concentrations with RSFC. We investigated the relationship between NAS, RSFC and cortical GABA+/Cr concentrations. Within the default mode network (DMN) an area of the dorsomedial prefrontal cortex (DMPFC) had greater connectivity with the rest of the DMN in PPD (peak voxel: MNI coordinates (2, 58, 32), p = 0.002) and was correlated to depression scores (peak HAM-D17 voxel: MNI coordinates (0, 60, 34), p = 0.008). pgACC GABA+/Cr correlated positively with DMPFC RSFC in a region spanning the right anterior/posterior insula and right temporal pole (r = +0.661, p = 0.000). OCC GABA+/Cr correlated positively with regions spanning both amygdalae (right amygdala: r = +0.522, p = 0.000; left amygdala: r = +0.651, p = 0.000) as well as superior parietal areas. Plasma allopregnanolone was higher in PPD (p = 0.03) and positively correlated with intra DMPFC connectivity (r = +0.548, p = 0.000) but not GABA+/Cr. These results provide initial evidence that PPD is associated with altered DMN connectivity; cortical GABA+/Cr concentrations are associated with postpartum RSFC and allopregnanolone is associated with postpartum intra-DMPFC connectivity.
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In brain regions associated with emotion and self-perception, neural network connectivity supported by GABAergic signaling is positively correlated with plasma allopregnanolone concentrations in individuals with postpartum depression versus healthy postpartum female individuals.
“In brain regions associated with emotion and self-perception, neural network connectivity, supported by GABAergic signaling, is positively correlated with plasma allopregnanolone concentrations in individuals with PPD vs healthy postpartum female individuals.33”
From Effect of Zuranolone vs Placebo in Postpartum Depression (2021) · cites this paper as [33]
The Demographic and clinical data section (p. 7) reports a positive correlation between postpartum allopregnanolone and intra-DMPFC connectivity in the PPD group, but not in healthy comparison women. The Discussion (p. 8) describes a GABA-mediated contribution as possible, not established; it also reports no correlation between allopregnanolone and measured cortical GABA concentrations. Thus the correlation is supported, but the asserted GABAergic mechanism is overstated. (LLM, conf=0.86)
Experimental — accuracy not yet measuredCortical GABAergic disinhibition in depressive disorders co-occurs with increases in glutamatergic gene expression in the default mode network (DMN).
“Specifically, cortical GABAergic disinhibition in depressive disorders co-occurs with increases in glutamatergic gene expression in the DMN [24,26,27,28,29,30,31,32].”
From Pharmacotherapies Targeting GABA-Glutamate Neurotransmission for Treatment-Resistant Depression (2023) · cites this paper as [26]
In women with TRD/treatment-resistant postpartum depression, depressive severity is linked to GABA concentrations in the DMN.
“In women with TRD/treatment-resistant postpartum depression, depressive severity is linked to GABA concentrations in the DMN [26,27].”
From Pharmacotherapies Targeting GABA-Glutamate Neurotransmission for Treatment-Resistant Depression (2023) · cites this paper as [26]
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Cites
The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research
Buysse, D. J., Reynolds, C. F., Monk, T. H., Berman, S. R., & Kupfer, D. J. (1989) · Psychiatry Research · doi:10.1016/0165-1781(89)90047-4 · Cited by 35,234 · see citing works
Detection of Postnatal Depression: Development of the 10-item Edinburgh Postnatal Depression Scale
Cox, J. L., Holden, J. M., & Sagovsky, R. (1987) · British Journal of Psychiatry · doi:10.1192/bjp.150.6.782 · Cited by 13,982 · see citing works
<i>The Brain's Default Network</i>: <i>Anatomy, Function, and Relevance to Disease</i>
Buckner, R. L., Andrews‐Hanna, J. R., & Schacter, D. L. (2008) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1440.011 · Cited by 9,761 · see citing works
Dissociable intrinsic connectivity networks for salience processing and executive control
Seeley, W. W., Menon, V., Schatzberg, A. F., Keller, J., Glover, G. H., Kenna, H., Reiss, A. L., & Greicius, M. D. (2007) · The Journal of Neuroscience · doi:10.1523/jneurosci.5587-06.2007 · Cited by 7,426 · see citing works
The precuneus: a review of its functional anatomy and behavioural correlates
Cavanna, A. E., & Trimble, M. R. (2006) · Brain · doi:10.1093/brain/awl004 · Cited by 5,128 · see citing works
Perinatal Depression: A Systematic Review of Prevalence and Incidence
Gavin, N. I., Gaynes, B. N., Lohr, K. N., Meltzer-Brody, S., Gartlehner, G., & Swinson, T. (2005) · Obstetrics & Gynecology · doi:10.1097/01.aog.0000183597.31630.db · Cited by 3,282 · see citing works
Spielberger, C. D. (2010) · The Corsini Encyclopedia of Psychology · doi:10.1002/9780470479216.corpsy0943 · Cited by 2,535 · see citing works
Kaiser, R. H., Andrews-Hanna, J. R., Wager, T. D., & Pizzagalli, D. A. (2015) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2015.0071 · Cited by 2,281 · see citing works
Wilamowska (2010) · doi:10.1001/archpsyc.1988.01800320058007 · Cited by 2,115 · see citing works
ICA-AROMA: A robust ICA-based strategy for removing motion artifacts from fMRI data
Pruim, R. H. R., Mennes, M., van Rooij, D., Llera, A., Buitelaar, J. K., & Beckmann, C. F. (2015) · NeuroImage · doi:10.1016/j.neuroimage.2015.02.064 · Cited by 1,684 · see citing works
Paul, S. M., & Purdy, R. H. (1992) · The FASEB Journal · doi:10.1096/fasebj.6.6.1347506 · Cited by 1,328 · see citing works
Sheline, Y. I., Price, J. L., Yan, Z., & Mintun, M. A. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1000446107 · Cited by 1,196 · see citing works
Adolphs, R., Damasio, H., Tranel, D., Cooper, G., & Damasio, A. R. (2000) · The Journal of Neuroscience · doi:10.1523/jneurosci.20-07-02683.2000 · Cited by 1,095 · see citing works
Mind reading: Neural mechanisms of theory of mind and self-perspective
Vogeley, K., Bussfeld, P., Newen, A., Herrmann, S., Happé, F., Falkai, P., Maier, W., Shah, N. J., Fink, G. R., & Zilles, K. (2001) · NeuroImage · doi:10.1006/nimg.2001.0789 · Cited by 998 · see citing works
Antenatal risk factors for postnatal depression: A large prospective study
Milgrom, J., Gemmill, A. W., Bilszta, J. L., Hayes, B., Barnett, B., Brooks, J., Ericksen, J., Ellwood, D., & Buist, A. (2008) · Journal of Affective Disorders · doi:10.1016/j.jad.2007.10.014 · Cited by 953 · see citing works
Purdy, R. H., Morrow, A. L., Moore, P. H., & Paul, S. M. (1991) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.88.10.4553 · Cited by 951 · see citing works
Sheehan, D. V. (1984) · Medical Entomology and Zoology · Cited by 883 · see citing works
Prevalence of suicidality during pregnancy and the postpartum
Lindahl, V., Pearson, J. L., & Colpe, L. (2005) · Archives of Women’s Mental Health · doi:10.1007/s00737-005-0080-1 · Cited by 795 · see citing works
Sanacora, G., Mason, G. F., Rothman, D. L., Behar, K. L., Hyder, F., Petroff, O. A. C., Berman, R. M., Charney, D. S., & Krystal, J. H. (1999) · Archives of General Psychiatry · doi:10.1001/archpsyc.56.11.1043 · Cited by 627 · see citing works
Edden, R. A. E., Puts, N. A. J., Harris, A. D., Barker, P. B., & Evans, J. (2013) · Journal of Magnetic Resonance Imaging · doi:10.1002/jmri.24478 · Cited by 625 · see citing works
Self-citationMenstrual cycle phase modulates reward-related neural function in women
Dreher, J.-C., Schmidt, P. J., Kohn, P., Furman, D., Rubinow, D., & Berman, K. F. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0605569104 · Cited by 567 · see citing works
Current practice in the use of MEGA-PRESS spectroscopy for the detection of GABA
Mullins, P. G., McGonigle, D. J., Tuura, R., Puts, N. A. J., Vidyasagar, R., Evans, J., & Edden, R. A. E. (2012) · NeuroImage · doi:10.1016/j.neuroimage.2012.12.004 · Cited by 555 · see citing works
Self-citationShear, M. K., Vander Bilt, J., Rucci, P., Endicott, J., Lydiard, B., Otto, M. W., Pollack, M. H., Chandler, L., Williams, J., Ali, A., et al. (2001) · Depression and Anxiety · doi:10.1002/da.1033 · Cited by 483 · see citing works
GABAAR Plasticity during Pregnancy: Relevance to Postpartum Depression
Maguire, J., & Mody, I. (2008) · Neuron · doi:10.1016/j.neuron.2008.06.019 · Cited by 437 · see citing works
Epperson, C. N., Haga, K. K., Mason, G. F., Sellers, E. M., Gueorguieva, R. V., Zhang, W., Weiss, E. L., Rothman, D. L., & Krystal, J. H. (2002) · Archives of General Psychiatry · doi:10.1001/archpsyc.59.9.851 · Cited by 402 · see citing works
Paul, S. M., & Purdy, R. H. (1992) · PubMed · Cited by 384 · see citing works
GABA concentrations in the human anterior cingulate cortex predict negative BOLD responses in fMRI
Northoff, G., Walter, M., Schulte, R. F., Beck, J., Dydak, U., Henning, A., Boeker, H., Grimm, S., & Boesiger, P. (2007) · Nature Neuroscience · doi:10.1038/nn2001 · Cited by 359 · see citing works
Putnam, K. T., Wilcox, M., Robertson‐Blackmore, E., Sharkey, K. M., Bergink, V., Munk‐Olsen, T., Deligiannidis, K. M., Payne, J. L., Altemus, M. M., Newport, D. J., et al. (2017) · The Lancet Psychiatry · doi:10.1016/s2215-0366(17)30136-0 · Cited by 308 · see citing works
Self-citationDuncan, N. W., Wiebking, C., & Northoff, G. (2014) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2014.07.016 · Cited by 220 · see citing works
Kapogiannis, D., Reiter, D. A., Willette, A. A., & Mattson, M. P. (2013) · NeuroImage · doi:10.1016/j.neuroimage.2012.09.029 · Cited by 211 · see citing works
Moses-Kolko, E. L., Perlman, S. B., Wisner, K. L., James, J., Saul, A. T., & Phillips, M. L. (2010) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2010.09081235 · Cited by 190 · see citing works
Familiality of Postpartum Depression in Unipolar Disorder: Results of a Family Study
Forty, L., Jones, L., MacGregor, S., Caesar, S., Cooper, C., Hough, A., Dean, L., Dave, S., Farmer, A., McGuffin, P., et al. (2006) · American Journal of Psychiatry · doi:10.1176/appi.ajp.163.9.1549 · Cited by 186 · see citing works
Baseline GABA concentration and fMRI response
Donahue, M. J., Near, J., Blicher, J. U., & Jezzard, P. (2010) · NeuroImage · doi:10.1016/j.neuroimage.2010.07.017 · Cited by 174 · see citing works
Deligiannidis, K. M., Şıkoğlu, E. M., Shaffer, S. A., Frederick, B. B., Svenson, A., Kopoyan, A., Kosma, C. A., Rothschild, A. J., & Moore, C. M. (2013) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2013.02.010 · Cited by 153 · see citing works
Self-citationPreliminary evidence of reduced occipital GABA concentrations in puerperal women: a 1H-MRS study
Epperson, C. N., Gueorguieva, R. V., Czarkowski, K. A., Stiklus, S. M., Sellers, E. M., Krystal, J. H., Rothman, D. L., & Mason, G. F. (2006) · Psychopharmacology · doi:10.1007/s00213-006-0313-7 · Cited by 145 · see citing works
Maternal Depressive Symptoms During and After Pregnancy and Psychiatric Problems in Children
Lahti‐Pulkkinen, M., Savolainen, K., Tuovinen, S., Pesonen, A., Lahti, J. M. T., Heinonen, K., Hämäläinen, E. K., Laivuori, H. M., Villa, P., Reynolds, R. M., et al. (2016) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1016/j.jaac.2016.10.007 · Cited by 139 · see citing works
GABA in the insula — a predictor of the neural response to interoceptive awareness
Wiebking, C., Duncan, N. W., Tiret, B., Hayes, D. J., Marjańska, M., Doyon, J., Bajbouj, M., & Northoff, G. (2013) · NeuroImage · doi:10.1016/j.neuroimage.2013.04.042 · Cited by 131 · see citing works
Waddell, K. W., Avison, M. J., Joers, J. M., et al. (2007) · Magnetic Resonance Imaging · doi:10.1016/j.mri.2006.11.026 · Cited by 124 · see citing works
Deligiannidis, K. M., Kroll‐Desrosiers, A., Mo, S., Nguyen, H. P., Svenson, A., Jaitly, N., Hall, J. E., BARTON, B. A., Rothschild, A. J., & Shaffer, S. A. (2016) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2016.05.010 · Cited by 114 · see citing works
Self-citationMeltzer-Brody, S. E., Boschloo, L., Jones, I. R., Sullivan, P. F., & Penninx, B. W. J. H. (2013) · Archives of Women s Mental Health · doi:10.1007/s00737-013-0372-9 · Cited by 103 · see citing works
Baller, E. B., Wei, S.-M., Kohn, P. D., Rubinow, D. R., Alarcón, G., Schmidt, P. J., & Berman, K. F. (2013) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2012.12030385 · Cited by 102 · see citing works
Spectral-editing measurements of GABA in the human brain with and without macromolecule suppression
Harris, A. D., Puts, N. A. J., Barker, P. B., & Edden, R. A. E. (2014) · Magnetic Resonance in Medicine · doi:10.1002/mrm.25549 · Cited by 95 · see citing works
Self-citationAnterior cingulate cortex γ-aminobutyric acid deficits in youth with depression
Gabbay, V., Bradley, K., Mao, X., Ostrover, R., Kang, G., & Shungu, D. C. (2017) · Translational Psychiatry · doi:10.1038/tp.2017.187 · Cited by 91 · see citing works
Duan, C., Cosgrove, J., & Deligiannidis, K. M. (2017) · Current Psychiatry Reports · doi:10.1007/s11920-017-0824-4 · Cited by 59 · see citing works
Self-citationHarris, A. D., Puts, N. A. J., Anderson, B. A., Yantis, S., Pekar, J. J., Barker, P. B., & Edden, R. A. E. (2015) · PLoS ONE · doi:10.1371/journal.pone.0117531 · Cited by 43 · see citing works
Self-citationZhao, C., & Gammie, S. C. (2014) · Brain Research · doi:10.1016/j.brainres.2014.10.023 · Cited by 35 · see citing works
Plasticity and function of extrasynaptic GABAA receptors during pregnancy and after delivery
Mostallino, M. C., Sanna, E., Concas, A., Biggio, G., & Follesa, P. (2009) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2009.06.013 · Cited by 32 · see citing works
Alterations in regional brain GABA concentration and turnover during pregnancy
Smolen, A., Smolen, T. N., & Han, P. C. (1993) · Pharmacology Biochemistry and Behavior · doi:10.1016/0091-3057(93)90281-w · Cited by 23 · see citing works
Hill, M., Pařı́zek, A., Klak, J., Hampl, R., Šulcová, J., Havlı́ková, H., Lapčı́k, O., Bičı́ková, M., Fait, T., Kancheva, R. L., et al. (2002) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/s0960-0760(02)00188-7 · Cited by 13 · see citing works
Flagged first, then by citations
Research works printed but not linked: 3
- [25]25. postpartum in maternal and umbilical blood: 3.3beta-hydroxy-5-ene steroids. J Steroid Biochem Mol Biol. 2002;82:241 -50.
- [31]31. First MB, Spitzer RL, Gibbon M, Williams JBW. Structured clinical interview for DSM-IV-TR axis I disorders -patient edition. New York, NY: Biometrics Research Department, New York State Psychiatric Institute; 2001.
- [32]32. Williams JB. A structured interview guide for the Hamilton Depression Rating Scale. Arch Gen Psychiatry. 1988;45:742 -7.
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“In women with TRD/treatment-resistant postpartum depression, depressive severity is linked to GABA concentrations in the DMN [26,27].”
BackgroundDeligiannidis, K. M., Kroll-Desrosiers, A. R., Tan, Y., Dubuke, M. L., & Shaffer, S. A. (2020) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2020.104827 · Cited by 31 · see citing works
Self-citation
- Authors
- Deligiannidis, K. M., Fales, C. L., Kroll-Desrosiers, A. R., Shaffer, S. A., Villamarin, V., Tan, Y., Hall, J. E., Frederick, B. B., Sikoglu, E. M., Edden, R. A., Rothschild, A. J., & Moore, C. M.
- Affiliations
- Northwell Health (US)
- University of Massachusetts Chan Medical School (US)
- National Institute of Environmental Health Sciences (US)
- Harvard University (US)
- Kennedy Krieger Institute (US)
- Corresponding author
- Deligiannidis, Kristina M.
- ORCID
- Venue
- Neuropsychopharmacology
- Published
- 2018-10-17
- Volume
- 44
- Issue
- 3
- Pages
- 546-554
- ISSN
- 0893-133X (ISSN-L)
- 1740-634X
- PMC
- PMC6333815
- OpenAlex
- W2891584849
- Cited by
- 92
- References
- 49
- Citations by year
- 2026: 7 · 2025: 14 · 2024: 14 · 2023: 15 · 2022: 11 · 2021: 11 · 2020: 12 · 2019: 8
- FWCI
- 7.39
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Neuropsychopharmacology (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- eScholarship@UMassChan (submittedVersion)
- Funders
- U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (K23MH097794)
- U.S. Department of Health & Human Services | National Institutes of Health (1S10RR027107, R01EB016089, P41EB015909)
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Maternal Mental Health During Pregnancy and Postpartum
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Keywords
- postpartum depression, resting-state functional connectivity, neurosteroids, allopregnanolone, pregenual anterior cingulate cortex, dorsomedial prefrontal cortex, default mode network, occipital cortex, amygdala, GABAergic neurotransmission
- MeSH terms
- Neurosteroids, Adult, Cerebral Cortex, Creatine, Female, gamma-Aminobutyric Acid, Gyrus Cinguli, Humans, Magnetic Resonance Imaging, Pregnanolone, Depression, Postpartum, Young Adult, Connectome, Proton Magnetic Resonance Spectroscopy
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